Beneficial Effect of Donepezil Augmentation for the Management of Comorbid Schizophrenia and Dementia

Abstract

Comorbid schizophrenia and dementia is a common clinical phenomenon; however, management of the coexisting illnesses remains incomplete. Donepezil, a cholinesterase inhibitor, may be beneficial for the management of symptoms of Alzheimer's disease, a disease in which cholinergic pathways in the cerebral cortex and basal forebrain are well known to be compromised. Furthermore, impaired cognition in elderly schizophrenic patients has been observed to be more than two thirds; however, there are no published controlled studies reporting the use of cholinesterase inhibitors in the management of schizophrenia in patients with associated dementia. In this study, six patients with chronic schizophrenia and comorbid dementia were administered donepezil, 5 mg, in single-blind fashion as augmentation to their standard antipsychotic medication for a 4-week period. Patients were evaluated with the Mini Mental State Examination (MMSE); Alzheimer's Disease Assessment Scale, Cognitive subscale; Positive and Negative Symptom Scale (PANSS); and the Clinical Global Impression (CGI) scales. A significant improvement was noted in MMSE scores (P < 0.01) and for CGI scores (P < 0.01). In addition, three patients demonstrated improvement on the PANSS. Donepezil appears to be an effective treatment for the management of symptoms of dementia accompanying patients with comorbid schizophrenia and dementia. Since cholinergic dysfunction may be present in some patients with schizophrenia, the authors' findings further demonstrate the possibility that this disorder may be managed with cholinergic medications as augmenting agents, at least in this specific subpopulation of patients with comorbid dementia. To confirm the findings of this preliminary trial, further investigation is mandated with a larger sample of subjects in the context of a double-blind medication trial.

Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats

“…To date, however, the data collected in the relatively small number of clinical studies that have been designed to evaluate the potential cognitive benefits of AChEIs in schizophrenia have been equivocal. For example, the beneficial effects of donepezil or rivastigmine on cognition in schizophrenics as add-on treatments to antipsychotics observed in small preliminary investigations, open-label studies and case reports (e.g., Buchanan et al, 2003;Stryjer et al, 2003;Lenzi et al, 2003) were not confirmed in larger randomized, doubleblind, and placebo controlled studies (see Friedman et al, 2002;Freudenreich et al, 2005;Sharma et al, 2006). In the case of galantamine, there are also several small studies that indicate a potential benefit to schizophrenic patients including a recent randomized, doubleblind clinical trial (N=8) where the AChEI improved short-term memory and attention in schizophrenic or schizoaffective patients who were stabilized on risperidone (Schubert et al, 2006).…”

Cholinesterase Inhibitors Ameliorate Behavioral Deficits Induced by MK-801 in Mice

“…In two open-label trials where donepezil was added to the ongoing treatment of schizophrenia subjects with atypical antipsychotic drugs, an improvement in manual dexterity (Buchanan et al, 2002) and in clinical measures of dementia (eg MMSE) (Stryjer et al, 2003) was observed. However, in double-blind studies of donepezil added to treatment with risperidone (Friedman et al, 2002) or clozapine (Stryjer et al, 2004), no beneficial effects were observed.…”

Towards a muscarinic hypothesis of schizophrenia

“…The addition of donepezil (5 mg) to the standard antipsychotic treatment in a small cohort of elderly subjects with schizophrenia was shown to cause a modest improvement in cognitive measurements. 125 In a subsequent study, the addition of donepezil to clozapine in a double-blind crossover design showed no overall effect. Still, three out of eight subjects improved in the total Positive and Negative Syndrome Scale-score during the donepezilphase.…”